tbuckley/cabot-search huggingface dataset:
IPOP: An Integrative Plant Multi-omics Platform for Cross-species Comparison and Evolutionary Study
Authors: Wenyue Huang, Xiaona Hu, Yanlin Ren, Minggui Song, Chuang Ma, Zhenyan Miao
Journal: Molecular Biology and Evolution (2023)

The advent of high-throughput sequencing technologies has led to the production of a significant amount of omics data in plants, which serves as valuable assets for conducting cross-species multi-omics comparative analysis. Nevertheless, the current dearth of comprehensive platforms providing evolutionary annotation information and multi-species multi-omics data impedes users from systematically and efficiently performing evolutionary and functional analysis on specific genes. In order to establish an advanced plant multi-omics platform that provides timely, accurate, and high-caliber omics information, we collected 7 distinct types of omics data from 6 monocots, 6 dicots, and 1 moss, and reanalyzed these data using standardized pipelines. Additionally, we furnished homology information, duplication events, and phylostratigraphic stages of 13 species to facilitate evolutionary examination. Furthermore, the integrative plant omics platform (IPOP) is bundled with a variety of online analysis tools that aid users in conducting evolutionary and functional analysis. Specifically, the Multi-omics Integration Analysis tool is available to consolidate information from diverse omics sources, while the Transcriptome-wide Association Analysis tool facilitates the linkage of functional analysis with phenotype. To illustrate the application of IPOP, we conducted a case study on the YTH domain gene family, wherein we observed shared functionalities within orthologous groups and discerned variations in evolutionary patterns across these groups. To summarize, the IPOP platform offers valuable evolutionary insights and multi-omics data to the plant sciences community, effectively addressing the need for cross-species comparison and evolutionary research platforms. All data and modules within IPOP are freely accessible for academic purposes (http://omicstudio.cloud:4012/ipod/).
Albuminuria in transthyretin cardiac amyloidosis: Prevalence, progression and prognostic importance
Authors: Adam Ioannou, Muhammad U. Rauf, Rishi K. Patel, Yousuf Razvi, Aldostefano Porcari, Ana Martinez‐Naharro, Lucia Venneri, Francesco Bandera, Ruta Virsinskaite, Tushar Kotecha, Dan Knight, Aviva Petrie, Carol Whelan, Ashutosh Wechalekar, Helen Lachmann, Philip N. Hawkins, Scott D. Solomon, Julian D. Gillmore, Marianna Fontana
Journal: European Journal of Heart Failure (2023)

Abstract Aims Transthyretin cardiac amyloidosis (ATTR‐CA) is an infiltrative cardiomyopathy that commonly presents with concomitant chronic kidney disease. Albuminuria is common in heart failure and associated with worse outcomes, but its prevalence and relationship to outcome in ATTR‐CA remains unclear. Methods and results A total of 1181 patients with ATTR‐CA were studied (mean age 78.1 ± 7.9 years; 1022 [86.5%] male; median estimated glomerular filtration rate 59 ml/min/1.73m 2 [interquartile range: 47–74]). Albuminuria was present in 563 (47.7%) patients (499 [88.6%] with microalbuminuria and 64 [11.4%] with macroalbuminuria). Patients with albuminuria had a more severe cardiac phenotype evidenced by higher serum cardiac biomarkers (median N‐terminal pro‐B‐type natriuretic peptide [NT‐proBNP]: 4027 ng/L [2173–6889] vs. 1851 ng/L [997–3209], p &lt; 0.001; median troponin T: 69 ng/L [46–101] vs. 48 ng/L [34–68], p &lt; 0.001) and worse echocardiographic indices of systolic (longitudinal strain: −10.0 ± 3.6% vs. −11.6 ± 3.8%, p &lt; 0.001) and diastolic function (E/e′: 17.5 ± 6.4 vs. 16.4 ± 6.7, p &lt; 0.001) than those with a normal urinary albumin to creatinine ratio (UACR). Microalbuminuria and macroalbuminuria were independently associated with mortality in the overall population (hazard ratio [HR] 1.47, 95% confidence interval [CI] 1.13–1.92, p = 0.005 and HR 1.87, 95% CI 1.15–3.05, p = 0.012, respectively). In a subgroup of patients ( n = 349) without concomitant hypertension, diabetes mellitus or chronic kidney disease, albuminuria was also associated with mortality (HR 2.98, 95% CI 1.72–5.17, p &lt; 0.001). At 12 months, 330 patients had a repeat UACR measurement; those in whom UACR increased by 30% or more ( n = 148, 44.8%) had an increased risk of mortality (HR 1.84, 95% CI 1.06–3.19, p = 0.030). Conclusions Albuminuria is common in patients with ATTR‐CA, and more prevalent in those with a more severe cardiac phenotype. Albuminuria at diagnosis and a significant increase in UACR during follow‐up are associated with mortality.
Targosomes: Anti-HER2 PLGA nanocarriers for bioimaging, chemotherapy and local photothermal treatment of tumors and remote metastases
Authors: E.N. Komedchikova, O.A. Kolesnikova, A.V. Syuy, V.S. Volkov, S.M. Deyev, M.P. Nikitin, V.O. Shipunova
Journal: Journal of Controlled Release (2023)
Effective delivery of miR-511-3p with mannose-decorated exosomes with RNA nanoparticles confers protection against asthma
Authors: Wei Tu, Xinyue Hu, Rongjun Wan, Xiaojun Xiao, Yingchun Shen, Prakhyath Srikaram, Sai Nithin Avvaru, Fuhan Yang, Fengmei Pi, Yufeng Zhou, Mei Wan, Peisong Gao
Journal: Journal of Controlled Release (2023)

Our previous studies have shown that miR-511-3p treatment has a beneficial effect in alleviating allergic airway inflammation. Here, we sought to explore its therapeutic potential in animal models and gain a deeper understanding of its therapeutic value for asthma. miR-511-3p knockout mice (miR-511-3p−/−) were generated by CRISPR/Cas and showed exacerbated airway hyper-responsiveness and Th2-associated allergic airway inflammation compared with wild-type (WT) mice after exposed to cockroach allergen. RNA nanoparticles with mannose decorated EV-miR-511-3p were also created by loading miR-511-3p mimics into the mannose decorated EVs with engineered RNA nanoparticle PRNA-3WJ (Man-EV-miR-511-3p). Intra-tracheal inhalation of Man-EV-miR-511-3p, which could effectively penetrate the airway mucus barrier and deliver functional miR-511-3p to lung macrophages, successfully reversed the increased airway inflammation observed in miR-511-3p−/− mice. Through microarray analysis, complement C3 (C3) was identified as one of the major targets of miR-511-3p. C3 was increased in LPS-treated macrophages but decreased after miR-511-3p treatment. Consistent with these findings, C3 expression was elevated in the lung macrophages of an asthma mouse model but decreased in mice treated with miR-511-3p. Further experiments, including miRNA-mRNA pulldown and luciferase reporter assays, confirmed that miR-511-3p directly binds to C3 and activates the C3 gene. Thus, miR-511-3p represents a promising therapeutic target for asthma, and RNA nanotechnology reprogrammed EVs are efficient carriers for miRNA delivery for disease treatment.
Periodontitis and atherosclerotic cardiovascular disease: A critical appraisal
Authors: Maria Clotilde Carra, Hélène Rangé, Giuseppina Caligiuri, Philippe Bouchard
Journal: Periodontology 2000 (2023)

Abstract In spite of intensive research efforts driving spectacular advances in terms of prevention and treatments, cardiovascular diseases (CVDs) remain a leading health burden, accounting for 32% of all deaths (World Health Organization. “Cardiovascular Diseases (CVDs).” WHO, February 1, 2017, https://www.who.int/news‐room/fact‐sheets/detail/cardiovascular‐diseases‐ (cvds)). Cardiovascular diseases are a group of disorders affecting the heart and blood vessels. They encompass a collection of different conditions, among which atherosclerotic cardiovascular disease (ASCVD) is the most prevalent. CVDs caused by atherosclerosis, that is, ASCVD, are particularly fatal: with heart attack and stroke being together the most prevalent cause of death in the world. To reduce the health burden represented by ASCVD, it is urgent to identify the nature of the “residual risk,” beyond the established risk factors (e.g., hypertension) and behavioral factors already maximally targeted by drugs and public health campaigns. Remarkably, periodontitis is increasingly recognized as an independent cardiovascular risk factor.
Physical activity and checkpoint inhibition: association with toxicity and survival
Authors: Rik J Verheijden, Anna Cabané Ballester, Karel C Smit, Mick J M van Eijs, Cheryl P Bruijnen, Anne S R van Lindert, Karijn P M Suijkerbuijk, Anne M May
Journal: JNCI Journal of the National Cancer Institute (2023)

Abstract Background Although animal experiments suggest beneficial effects of physical activity (PA) on antitumor immunity, little is known about the effects of PA on immune checkpoint inhibitor (ICI) toxicity and effectiveness in humans. We assessed the association of PA with immune-related adverse events (irAE) and survival in patients undergoing ICI. Methods Patients receiving ICI who completed the Dutch short questionnaire to assess health enhancing physical activity (SQUASH) questionnaire at the start of treatment as part of the prospective UNICIT study in an academic hospital were included. PA was quantified by calculating total metabolic equivalent task hours per week (total PA) and hours per week of moderate- to vigorous-intensity PA during sport and leisure time (MVPA-SL). Associations of PA with severe irAE occurrence within 1 year and overall survival (OS) were evaluated using logistic regression and Cox proportional hazard regression, respectively, with adjustment for probable confounders. Results In total, 251 patients were included, with a median follow-up of 20 months. Moderate and high levels of total PA were associated with lower odds of severe irAE occurrence compared to low levels of total PA (adjusted OR: 0.34 [95% CI = 0.12 to 0.90] and 0.19 [95% CI = 0.05 to 0.55], respectively). Moderate and high levels of total PA were also associated with prolonged survival (adjusted HR: 0.58 [95% CI = 0.32 to 1.04] and 0.48 [95% CI = 0.27 to 0.89], respectively). Similar associations were observed in patients who performed more MVPA-SL. Conclusions Higher physical activity levels at the start of ICI treatment are associated with lower risk of severe irAEs and probably prolonged survival. Randomized controlled trials are needed to investigate whether patients indeed benefit from increasing PA levels after diagnosis.
Treatment-related adverse events, including fatal toxicities, in patients with solid tumours receiving neoadjuvant and adjuvant immune checkpoint blockade: a systematic review and meta-analysis of randomised controlled trials
Authors: Yu Fujiwara, Nobuyuki Horita, Elio Adib, Susu Zhou, Amin H Nassar, Zain UL Abideen Asad, Alessio Cortellini, Abdul Rafeh Naqash
Journal: The Lancet Oncology (2023)
Targeting GPR65 alleviates hepatic inflammation and fibrosis by suppressing the JNK and NF-κB pathways
Authors: Kun Zhang, Meng-Xia Zhang, Xiao-Xiang Meng, Jing Zhu, Jia-Jun Wang, Yi-Fan He, Ye-Hua Li, Si-Cong Zhao, Zhe-Min Shi, Li-Na Zheng, Tao Han, Wei Hong
Journal: Military Medical Research (2023)

G-protein coupled receptors (GPCRs) are recognized as attractive targets for drug therapy. However, it remains poorly understood how GPCRs, except for a few chemokine receptors, regulate the progression of liver fibrosis. Here, we aimed to reveal the role of GPR65, a proton-sensing receptor, in liver fibrosis and to elucidate the underlying mechanism. The expression level of GPR65 was evaluated in both human and mouse fibrotic livers. Furthermore, Gpr65-deficient mice were treated with either bile duct ligation (BDL) for 21 d or carbon tetrachloride (CCl4) for 8 weeks to investigate the role of GPR65 in liver fibrosis. A combination of experimental approaches, including Western blotting, quantitative real-time reverse transcription‑polymerase chain reaction (qRT-PCR), and enzyme-linked immunosorbent assay (ELISA), confocal microscopy and rescue studies, were used to explore the underlying mechanisms of GPR65's action in liver fibrosis. Additionally, the therapeutic potential of GPR65 inhibitor in the development of liver fibrosis was investigated. We found that hepatic macrophages (HMs)-enriched GPR65 was upregulated in both human and mouse fibrotic livers. Moreover, knockout of Gpr65 significantly alleviated BDL- and CCl4-induced liver inflammation, injury and fibrosis in vivo, and mouse bone marrow transplantation (BMT) experiments further demonstrated that the protective effect of Gpr65 knockout is primarily mediated by bone marrow-derived macrophages (BMMs). Additionally, in vitro data demonstrated that Gpr65 silencing and GPR65 antagonist inhibited, while GPR65 overexpression and application of GPR65 endogenous and exogenous agonists enhanced the expression and release of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and transforming growth factor-β (TGF-β), all of which subsequently promoted the activation of hepatic stellate cells (HSCs) and the damage of hepatocytes (HCs). Mechanistically, GPR65 overexpression, the acidic pH and GPR65 exogenous agonist induced up-regulation of TNF-α and IL-6 via the Gαq-Ca2+-JNK/NF-κB pathways, while promoted the expression of TGF-β through the Gαq-Ca2+-MLK3-MKK7-JNK pathway. Notably, pharmacological GPR65 inhibition retarded the development of inflammation, HCs injury and fibrosis in vivo. GPR65 is a major regulator that modulates the progression of liver fibrosis. Thus, targeting GPR65 could be an effective therapeutic strategy for the prevention of liver fibrosis.
Diagnosis and preoperative evaluation of vena cava mass by endoscopic ultrasound: “hunting” for the overlooked lesions
Authors: JinYu Wu, JiaYun Xu, ZengMin Zong, CuiWei Zhang, Huan Xu, Lei Shi
Journal: Endoscopy (2023)

A 53-year-old woman was admitted to our hospital with right-sided lower abdominal pain lasting for 1 year. Her laboratory tests were unremarkable. Computed tomography (CT) and CT angiography revealed a 4.7 × 4.0 × 5.4 cm mass along the posterior head of the pancreas and invading the inferior vena cava (IVC) ([Fig. 1], [Video 1]). Endoscopic ultrasound (EUS) found a solid hypoechoic lesion separate from the pancreas, which was growing transmurally and partially protruding outside the IVC wall and encroaching upon the right renal and hepatic veins. For a definitive diagnosis, we performed EUS-guided fine-needle aspiration (EUS-FNA) of the tissue mass through the duodenum, using a 22-gauge needle ([Fig. 2]).
Enhancing near-infrared II photodynamic therapy with nitric oxide for eradicating multidrug-resistant biofilms in deep tissues
Authors: Fanqiang Bu, Xiaoxu Kang, Dongsheng Tang, Fang Liu, Lin Chen, Pengfei Zhang, Wenli Feng, Yingjie Yu, Guofeng Li, Haihua Xiao, Xing Wang
Journal: Bioactive Materials (2023)

Nitric oxide (NO) enhanced photodynamic therapy (PDT) is a promising approach to overcome drug tolerance and resistance to biofilm but is limited by its short excitation wavelengths and low yield of reactive oxygen species (ROS). Herein, we develop a compelling degradable polymer-based near-infrared II (NIR-II, 1000-1700 nm) photosensitizer (PNIR-II), which can maintain 50 % PDT efficacy even under a 2.6 cm tissue barrier. Remarkably, PNIR-II is synthesized by alternately connecting the electron donor thiophene to the electron acceptors diketopyrrolopyrrole (DPP) and boron dipyrromethene (BODIPY), where the intramolecular charge transfer properties can be tuned to increase the intersystem crossover rate and decrease the internal conversion rate, thereby stabilizing the NIR-II photodynamic rather than photothermal effect. For exerting a combination therapy to eradicate multidrug-resistant biofilms, PNIR-II is further assembled into nanoparticles (NPs) with a synthetic glutathione-triggered NO donor polymer. Under 1064 nm laser radiation, NPs precisely release ROS and NO that triggered by over-expressed GSH in the biofilm microenvironment, thereby forming more bactericidal reactive nitrogen species (RNS) in vitro and in vivo in the mice model that orderly destroy biofilm of multidrug-resistant Staphylococcus aureus cultures from clinical patients. It thus provides a new outlook for destroy the biofilm of deep tissues.
Prognostic implications of CD9 in childhood acute lymphoblastic leukemia: insights from a nationwide multicenter study in China
Authors: Kam Tong Leung, Jiaoyang Cai, Yu Liu, Kathy Yuen Yee Chan, Jingbo Shao, Hui Yang, Qun Hu, Yao Xue, Xuedong Wu, Xia Guo, Xiaowen Zhai, Ningling Wang, Xue Li, Xin Tian, Zheng Li, Ning Xue, Yuxia Guo, Lingzhen Wang, Yao Zou, Peifang Xiao, Yingyi He, Runming Jin, Jingyan Tang, Jun J. Yang, Shuhong Shen, Ching-Hon Pui, Chi Kong Li
Journal: Leukemia (2023)

Abstract The outcomes of children with acute lymphoblastic leukemia (ALL) have been incrementally improved with risk-directed chemotherapy but therapy responses remain heterogeneous. Parameters with added prognostic values are warranted to refine the current risk stratification system and inform appropriate therapies. CD9, implicated by our prior single-center study, holds promise as one such parameter. To determine its precise prognostic significance, we analyzed a nationwide, multicenter, uniformly treated cohort of childhood ALL cases, where CD9 status was defined by flow cytometry on diagnostic samples of 3781 subjects. CD9 was expressed in 88.5% of B-ALL and 27.9% of T-ALL cases. It conferred a lower 5-year EFS and a higher CIR in B-ALL but not in T-ALL patients. The prognostic impact of CD9 was most pronounced in the intermediate/high-risk arms and those with minimal residual diseases, particularly at day 19 of remission induction. The adverse impact of CD9 was confined to specific cytogenetics, notably BCR::ABL1 + rather than KMT2A -rearranged leukemia. Multivariate analyses confirmed CD9 as an independent predictor of both events and relapse. The measurement of CD9 offers insights into patients necessitating intervention, warranting its seamless integration into the diagnostic marker panel to inform risk level and timely introduction of therapeutic intervention for childhood ALL.
An explainable machine learning-based phenomapping strategy for adaptive predictive enrichment in randomized clinical trials
Authors: Evangelos K. Oikonomou, Phyllis M. Thangaraj, Deepak L. Bhatt, Joseph S. Ross, Lawrence H. Young, Harlan M. Krumholz, Marc A. Suchard, Rohan Khera
Journal: npj Digital Medicine (2023)

Abstract Randomized clinical trials (RCT) represent the cornerstone of evidence-based medicine but are resource-intensive. We propose and evaluate a machine learning (ML) strategy of adaptive predictive enrichment through computational trial phenomaps to optimize RCT enrollment. In simulated group sequential analyses of two large cardiovascular outcomes RCTs of (1) a therapeutic drug (pioglitazone versus placebo; Insulin Resistance Intervention after Stroke (IRIS) trial), and (2) a disease management strategy (intensive versus standard systolic blood pressure reduction in the Systolic Blood Pressure Intervention Trial (SPRINT)), we constructed dynamic phenotypic representations to infer response profiles during interim analyses and examined their association with study outcomes. Across three interim timepoints, our strategy learned dynamic phenotypic signatures predictive of individualized cardiovascular benefit. By conditioning a prospective candidate’s probability of enrollment on their predicted benefit, we estimate that our approach would have enabled a reduction in the final trial size across ten simulations (IRIS: −14.8% ± 3.1%, p one-sample t-test = 0.001; SPRINT: −17.6% ± 3.6%, p one-sample t-test &lt; 0.001), while preserving the original average treatment effect (IRIS: hazard ratio of 0.73 ± 0.01 for pioglitazone vs placebo, vs 0.76 in the original trial; SPRINT: hazard ratio of 0.72 ± 0.01 for intensive vs standard systolic blood pressure, vs 0.75 in the original trial; all simulations with Cox regression-derived p value of &lt; 0.01 for the effect of the intervention on the respective primary outcome). This adaptive framework has the potential to maximize RCT enrollment efficiency.
Digital health application integrating wearable data and behavioral patterns improves metabolic health
Authors: Ashkan Dehghani Zahedani, Tracey McLaughlin, Arvind Veluvali, Nima Aghaeepour, Amir Hosseinian, Saransh Agarwal, Jingyi Ruan, Shital Tripathi, Mark Woodward, Noosheen Hashemi, Michael Snyder
Journal: npj Digital Medicine (2023)

Abstract The effectiveness of lifestyle interventions in reducing caloric intake and increasing physical activity for preventing Type 2 Diabetes (T2D) has been previously demonstrated. The use of modern technologies can potentially further improve the success of these interventions, promote metabolic health, and prevent T2D at scale. To test this concept, we built a remote program that uses continuous glucose monitoring (CGM) and wearables to make lifestyle recommendations that improve health. We enrolled 2,217 participants with varying degrees of glucose levels (normal range, and prediabetes and T2D ranges), using continuous glucose monitoring (CGM) over 28 days to capture glucose patterns. Participants logged food intake, physical activity, and body weight via a smartphone app that integrated wearables data and provided daily insights, including overlaying glucose patterns with activity and food intake, macronutrient breakdown, glycemic index (GI), glycemic load (GL), and activity measures. The app furthermore provided personalized recommendations based on users’ preferences, goals, and observed glycemic patterns. Users could interact with the app for an additional 2 months without CGM. Here we report significant improvements in hyperglycemia, glucose variability, and hypoglycemia, particularly in those who were not diabetic at baseline. Body weight decreased in all groups, especially those who were overweight or obese. Healthy eating habits improved significantly, with reduced daily caloric intake and carbohydrate-to-calorie ratio and increased intake of protein, fiber, and healthy fats relative to calories. These findings suggest that lifestyle recommendations, in addition to behavior logging and CGM data integration within a mobile app, can enhance the metabolic health of both nondiabetic and T2D individuals, leading to healthier lifestyle choices. This technology can be a valuable tool for T2D prevention and treatment.
Juggling Two Full-Time Jobs — Methadone Clinic Engagement and Cancer Care
Authors: Katie F. Jones, Paul Joudrey, Diane Meier, Salimah Meghani, Jessica Merlin
Journal: New England Journal of Medicine (2023)

When Mr. C. is diagnosed with head and neck cancer, he discovers that undergoing cancer care while engaged in the methadone-clinic system is far more complicated than it should be.
Implementing quality management systems to close the AI translation gap and facilitate safe, ethical, and effective health AI solutions
Authors: Shauna M. Overgaard, Megan G. Graham, Tracey Brereton, Michael J. Pencina, John D. Halamka, David E. Vidal, Nicoleta J. Economou-Zavlanos
Journal: npj Digital Medicine (2023)

The integration of Quality Management System (QMS) principles into the life cycle of development, deployment, and utilization of machine learning (ML) and artificial intelligence (AI) technologies within healthcare settings holds the potential to close the AI translation gap by establishing a robust framework that accelerates the safe, ethical, and effective delivery of AI/ML in day-to-day patient care. Healthcare organizations (HCOs) can implement these principles effectively by embracing an enterprise QMS analogous to those in regulated industries. By establishing a QMS explicitly tailored to health AI technologies, HCOs can comply with evolving regulations and minimize redundancy and rework while aligning their internal governance practices with their steadfast commitment to scientific rigor and medical excellence.